Injury necrotic cell death following

The mechanisms of the changes in cell viability during renal injury are incompletely understood. Most of the experimental data have been derived from the ischemia-reperfusion model of acute kidney injury and have focused on necrotic cell death. Because as many as 50% of patients have ischemia-induced acute kidney injury, the observations should be relevant to a large portion of the patients at risk. Also, different stresses initiate common biochemical events, so that understanding the relevant pathways of one stress will most likely be apphcable to others. What follows is a detailed analysis of some of the pathways currently thought to execute cell death in a variety of nephrotoxic insults. 

Cysteine proteases, called calpains, are known to be activated by sustained elevations in intracellular free calcium. Once activated, calpains degrade the cytoskeleton, transmitter and membrane channels, and metabolic enzymes (Hou and MacManus 2002 Mattson 2003 Nicholls 2004). Functionally, calpains have been characterized as pivotal mediators of both active necrotic cell death and PCD (Wang 2000) following cell-damaging stressors and insults such as soman exposure, excitotoxic challenges, toxins, free radicals, UV radiation, acute hypoxia, traumatic brain injury, cytokines, heat, and in chronic neurodegenerative conditions (Fischer et al. 1991 Caner et al. 

Hepatocyte death following APAP intake is the critical event in the clinical manifestation of liver injury. Hepatotoxic doses of APAP are believed to mainly cause necrotic cell death in hepatocytes (Gujral et al. 2002), predominantly in the centrilobar regions of liver. Apoptotic death or programmed ceU death has been... 

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